Phorbol ester pharmaceutical compositions and their use for treating inflammation

Abstract

The present invention relates to a method of inhibiting the protein kinase C-mediated biological response inflammation. The method comprises administering to a mammal a non-tumor promoting 12-deoxyphorbol ester. Phorbol esters suitable for use in the method include 12-deoxyphorbol 13-monoesters wherein the ester is a formate, acetate, propionate, butyrate, pentanoate, hexanote, benzoate or phenylacetate ester. The invention also relates to novel 12-deoxyphorbol 13-monoesters, wherein the ester can be a formate, propionate, butyrate or pentanoate ester, and to pharmaceutical compositions comprising same.

What is claimed is: 
     
       1. A pharmaceutical composition comprising a 12-deoxyphorbol 13-monoester, wherein the ester is a formate, acetate, propionate, butyrate, pentanoate, hexanoate, benzoate, or phenyl acetate ester, in an amount sufficient to treat inflammation, together with a pharmaceutically acceptable carrier. 
     
     
       2. The pharmaceutical composition of claim 1, wherein said composition is in dosage unit form. 
     
     
       3. A pharmaceutical composition comprising a 12-deoxyphorbol 13-monoester, wherein the ester is a formate, acetate, propionate, butyrate, pentanoate, hexanoate, benzoate, or phenyl acetate ester, in an amount sufficient to treat inflammation, together with a pharmaceutically acceptable carrier, wherein said carrier is not a volatile organic solvent. 
     
     
       4. A pharmaceutical composition comprising a 12-deoxyphorbol 13-monoester, wherein the ester is a formate, acetate, propionate, butyrate, pentanoate, hexanoate, benzoate, or phenyl acetate ester, in an amount sufficient to treat inflammation, together with a pharmaceutically acceptable carrier, wherein said composition is in dosage unit form. 
     
     
       5. A pharmaceutical composition comprising a 12-deoxyphorbol 13-monoester, wherein the ester is a formate, acetate, propionate, butyrate, pentanoate, hexanoate, benzoate, or phenyl acetate ester, in an amount sufficient to treat inflammation, together with a pharmaceutically acceptable carrier, wherein said composition is in the form of a lotion, gel, ointment, or cream. 
     
     
       6. A method of treating inflammation in a mammal in need thereof comprising administering to said mammal a 12-deoxyphorbol 13-monoester that is effective in the treatment of inflammation in an effective amount to treat said inflammation. 
     
     
       7. The method according to claim 6, wherein said ester is a formate, acetate, propionate, butyrate, pentanoate, hexanoate, benzoate, or phenyl acetate ester. 
     
     
       8. The method of claim 6, wherein said ester is an acetate ester. 
     
     
       9. The method of claim 6, wherein said ester is a formate, propionate, butyrate, or pentanoate ester. 
     
     
       10. The method of claim 6, wherein said ester is an acetate or phenyl acetate ester. 
     
     
       11. The method of claim 6, wherein said inflammation is dependent on a protein kinase C-mediated biological response. 
     
     
       12. The method of claim 6, wherein said inflammation is psoriasis. 
     
     
       13. The method of claim 6, wherein said inflammation is selected from the group consisting of seborrheic dermatitis, chloracne, atopic dermatitis, allergic contact dermatitis, lichen simplex chronicus, eczematous dermatitis, erythema multiforme, cutaneous lupus erythematosus, panniculitis, subacute inflammation, and chronic inflammation.